Quantification of endogenous Angiotensin 1-10, 1-9, 1-8, 1-7, and 1-5 in human plasma using micro-UHPLC-MS/MS: Outlining the importance of the pre-analytics for reliable results.

Angiotensin peptides (ANGs) play a central role in the renin-angiotensin-aldosterone system, rendering them interesting biomarkers associated with hypertension. Precise quantification of circulating ANGs holds the potential to assess the activity of angiotensin-converting enzyme (ACE), a key protease targeted by widely prescribed drugs, namely ACE inhibitors. This ability could pave the way for personalised medicine, offering insights into the prescription of inhibitors targeting either the proteases or the receptors within the system. Despite recent developments in liquid chromatography-mass spectrometry (LC-MS) methods for measuring circulating ANG concentrations, comprehensive stability studies of ANGs in human plasma are absent in the literature, raising concerns about the reliability of measured concentrations and their link to clinical conditions. To address this critical gap, we conducted an exhaustive evaluation of the pre-analytical stability of ANG1-10, ANG1-9, ANG1-8, ANG1-7, and ANG1-5. By employing surfactants to mitigate non-specific adsorption and a dedicated mix of protease inhibitors to limit protease activity, we established an MS-based assay for these five peptides. We used this method to quantify circulating concentrations of ANGs in the plasma of 11 healthy donors and 3 patients under kidney dialysis. Our findings revealed that ANG1-10 and ANG1-8 circulate at concentrations ranging from 1 to 10 pM in healthy subjects and exhibit a high degree of correlation. Notably, ANG1-9, ANG1-7, and ANG1-5 were undetectable in any of the 14 patients, despite a sub-picomolar limit of detection. This strikingly contrasts with the reference concentrations reported in the literature, which typically fall within the picomolar range. In light of these discrepancies, we strongly advocate for rigorous pre-analytical considerations and comprehensive stability studies to ensure reliable results. We emphasise the pivotal role of heightened pre-analytical awareness within the clinical chemistry community, and we hope for continued growth in this critical area.

Glomerular diseases in pregnancy: pragmatic recommendations for clinical management.

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage. An international working group undertook the review of available current literature and elicited expert opinions on glomerular diseases in pregnancy with the aim to provide pragmatic information for nephrologists according to the present state-of-the-art knowledge. This work also highlights areas of clinical uncertainty and emphasizes the need for further collaborative studies to improve maternal and fetal health.

Saxagliptin: A potential doping agent? A randomized, double-blinded, placebo-controlled, and crossover pilot study in young active men.

Neuropeptide Ys (NPYs) contribute to sympathetic-adreno stimulation: NPY1-36 potentiates the effects of catecholamines (CATs), whereas NPY3-36 inhibits CAT release. We sought to investigate whether inhibiting dipeptidyl-peptidase-4 (DPP4), cleaving NPY1-36 into NPY3-36, leads to increased NPY1-36 potentiating effects and reduced NPY3-36 inhibitory effects on CATs, thereby improving endurance performance. Seven male participants (age 27 ± 3 years, BMI 23.1 ± 2.4 kg/m2 ) performed time-to-exhaustion cycling exercise at 95% of peak power output with either placebo, or saxagliptin, a DPP4 inhibitor. Oxygen consumption (V̇O2 ), heart rate variability, NPY1-36, NPY3-36, catecholamines, and lactate were measured at several time points before, during, and after exercise. With saxagliptin, DPP4 activity (12.7 ± 1.6 vs. 0.2 ± 0.3 U/L, p = 0.001; d = 10.7) was decreased at rest, while NPY3-36 (1.94 ± 0.88 vs. 0.73 ± 0.22 pm; p < 0.001; d = 2.04) decreased and NPY1-36 increased during exercise (2.64 ± 2.22 vs. 4.59 ± 2.98 pm; p < 0.01; d = 0.19). CATs were unchanged. Time-to-exhaustion was 32% higher with saxagliptin. The difference in time-to-exhaustion between placebo and saxagliptin was correlated with NPY1-36 differences (R = 0.78, p < 0.05). Peak V̇O2 and other cardio-respiratory values were not different, whereas peak NPY concentrations were higher with saxagliptin. DPP4 blockade improved performance, increased NPY1-36, and decreased NPY3-36 concentrations which may have potentiating effects on the influences of CATs. However, DPP4 is involved in many different actions, thus NPYs are one group of factors that may underly its performance-enhancing effects; further studies are required to determine the exact mechanisms.

Medication Adherence Evaluated Through Electronic Monitors During the 2020 COVID-19 Pandemic Lockdown in Switzerland: A Longitudinal Analysis.

Background: During the 2020 COVID-19 lockdown, patients included in the Interprofessional Medication Adherence Program (IMAP) in Switzerland continued to use electronic monitors (EMs) that registered daily drug-dose intake. We aimed to understand to what extent patients' medication implementation (ie, the extent to which the patient took the prescribed medicine), measured with EMs, was impacted by the lockdown. Methods: Patients participating in the IMAP were diagnosed with diabetic kidney disease (DKD), solid cancer, human immunodeficiency virus (HIV) and miscellaneous long-term diseases (MLTD). Patient implementation was defined through a proxy: if all patient EMs were opened at least once daily, implementation was considered active (=1), and no implementation was considered (=0) otherwise. Implementation before (from December 2019 to March 2020), during (March to June 2020) and after (June to September 2020) the lockdown was compared. Subanalyses were performed according to the patients' diseases. Subanalyses were performed in patients who used at least one EM in 2018-2019 during the same periods (defined as winter, spring and summer). The logistic regression models used to estimate medication implementation according to the period were fitted using generalized estimating equations. Results: In 2020, patient implementation (n = 118) did not differ significantly before versus during (OR = 0.98, 95% CI: 0.84-1.15, p = 0.789) and before versus after (OR = 0.91, 95% CI: 0.79-1.06, p = 0.217) the lockdown. These findings remained stable when separately analyzing the implementation of patients with HIV (n = 61), DKD (n = 25) or MLTD (n = 22). Too few patients with cancer were included (n = 10) to interpret the results. In 2019, the implementation of 61/118 (51.7%) patients was significantly lower during summertime versus wintertime (OR = 0.73, 95% CI: 0.60-0.89, p = 0.002). Conclusion: Medication implementation remained steady before, during and after the lockdown in 2020. The IMAP before, during and after the lockdown may have supported the adherence of most patients, by ensuring continuity of care during periods of routine disturbances.

Understanding reasons and factors for participation and non-participation to a medication adherence program for patients with diabetic kidney disease in Switzerland: a mixed methods study.

BACKGROUND: An interprofessional medication adherence intervention led by pharmacists, combining motivational interviews and feedback with electronic monitor (EM) drug assessment, was offered to all consecutive patients with diabetic kidney disease (DKD) (estimated glomerular filtration rate < 60 mL/min/1.73 m2) visiting their nephrologist or endocrinologist. Approximately 73% (202/275) of eligible patients declined to participate, and the factors and reasons for refusal were investigated. METHODS: Sociodemographic and clinical data of included patients and those who refused were collected retrospectively for those who had previously signed the general consent form. Multivariate logistic regression analysis was performed to identify independent variables associated with non-participation. Patients who refused or accepted the adherence study were invited to participate in semi-structured interviews. Verbatim transcription, thematic analysis, and inductive coding were performed. RESULTS: Patients who refused to participate were older (n = 123, mean age 67.7 years, SD:10.4) than those who accepted (n = 57, mean age 64.0 years, SD:10.0, p = 0.027) and the proportion of women was higher among them than among patients who accepted it (30.9% vs 12.3%, p = 0.007). The time from diabetes diagnosis was longer in patients who refused than in those who accepted (median 14.2 years IQR 6.9-22.7 vs. 8.6 years, IQR 4.5-15.9, p = 0.003). Factors associated with an increased risk of non-participation were female sex (OR 3.8, 95% CI 1.4-10.0, p = 0.007) and the time from diabetes diagnosis (OR 1.05, 95% CI 1.01-1.09, p = 0.019). The included patients who were interviewed (n = 14) found the interprofessional intervention useful to improve their medication management, support medication literacy, and motivation. Patients who refused to participate and who were interviewed (n = 16) explained no perceived need, did not agree to use EM, and perceived the study as a burden and shared that the study would have been beneficial if introduced earlier in their therapeutic journey. Other barriers emerged as difficult relationships with healthcare providers, lack of awareness of the pharmacist's role, and negative perception of clinical research. CONCLUSIONS: Investigating the factors and reasons for participation and non-participation in a study helps tailor intervention designs to the needs of polypharmacy patients. Patients who refused the adherence intervention may not be aware of the benefits of medication management and medication literacy. There is an urgent need to advocate for interprofessional outpatient collaborations to support medication adherence in patients with DKD. Trial registration Clinicaltrials.gov NCT04190251_PANDIA IRIS.

Proneuropeptide Y and neuropeptide Y metabolites in healthy volunteers and patients with a pheochromocytoma or paraganglioma.

Neuropeptide Y (NPY1-36) is a vasoconstrictor peptide co-secreted with catecholamines by sympathetic nerves, the adrenal medulla, and neoplasms such as pheochromocytomas and paragangliomas (PPGLs). It is produced by the intracellular cleavage of proNPY and metabolized into multiple fragments with distinct biological activities. NPY immunoassays for PPGL have a diagnostic sensitivity ranging from 33 to 100%, depending on the antibody used. We have validated a multiplex micro-UHPLC-MS/MS assay for the specific and sensitive quantification of proNPY, NPY1-39, NPY1-37, NPY1-36, NPY2-36, NPY3-36, NPY1-35, NPY3-35, and the C-flanking peptide of NPY (CPON) (collectively termed NPYs), and determined the NPYs reference intervals and concentrations in 32 PPGL patients before, during, and after surgery. Depending on the peptide measured, NPYs were above the upper reference limit (URL) in 20% to 67% of patients, whereas plasma free metanephrine and normetanephrine, the gold standard for PPGL, were above the URL in 40% and 87% of patients, respectively. Age, sex, tachycardia, and tumor localization were not correlated with NPYs. Plasma free metanephrines performed better than NPYs in the detection of PPGL, but NPYs may be a substitute for an early diagnosis of PPGL for patients that suffer from severe kidney impairment or receiving treatments that interfere with catecholamine reuptake.

Bariatric Surgery Induces a Differential Effect on Plasma Aldosterone in Comparison to Dietary Advice Alone.

Background and Objectives: The pathophysiological mechanisms linking weight loss to blood pressure (BP) reduction are not completely understood. The objective of this study was to compare the effect of weight loss after Roux-en-Y gastric bypass (RYGB) on BP, renin-angiotensin-aldosterone system (RAAS), and urinary electrolytes excretion to those of dietary advice. Methods: This was a case-control prospective study including obese patients referred for RYGB (cases) and obese receiving diet advice only (controls). Ambulatory BP, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary electrolytes were measured before (M0) and after intervention (M3: 3 months and M12: 12 months). Results: Twenty-five patients were included in the RYGB group and twelve patients in the control group. After 12 months, weight loss (-42 ± 11.5 vs -12.3 ± 6.3 kg in the control group, p=0.001) and decrease in PAC were more pronounced in the RYGB group (-34 ± 76 vs +14 ± 45 pg/ml in the control group, p=0.002). There was no difference in PRA between both groups (-0.08 ± 1.68 vs 0.01 ± 0.37 ng/ml/h, p=0.31). Sodium excretion was more marked in the RYGB group after 3 months only (-89 ± 14.9 vs -9.9 ± 27.9 mmol/day, p=0.009). The decrease in SBP was similar between both groups (-6.9 ± 9.9 vs -7.1 ± 11.9 mmHg in the control group, p=0.96). Conclusions: Bariatric-induced weight loss induces a progressive decrease in PAC independently of PRA and sodium excretion. Whether this decrease in PAC affects target organ damage in the long term remains to be determined. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02218112.

[Severe asymptomatic hypertension and hypertensive emergency : From the ambulatory care to the emergency room]. / Hypertension artérielle sévère ou urgence hypertensive : du cabinet à l'hôpital.

High blood pressure levels are frequently encountered in medical practice, whether in an outpatient or inpatient setting. It is imperative to quickly differentiate severe hypertension associated with target organ damage, from severe hypertension without acute organ damage. In the latter situation, the management can be done on an outpatient basis by prescribing oral antihypertensive treatment with a close follow-up. On the other hand, in severe hypertension with acute target organ damage, patients should be admitted in an intensive care unit for close monitoring and, in most cases, treated with intravenous antihypertensive treatment. This article reviews the new definitions and management of these two entities and is addressed to both general practitioner and emergency doctor.

Les élévations sévères de la tension artérielle sont fréquemment rencontrées dans la pratique médicale, qu'elle soit ambulatoire ou hospitalière. Il est impératif de différencier rapidement une HTA sévère associée à un dommage d'organe(s) cible(s) d'une HTA sévère isolée. En effet, dans cette dernière situation, la prise en charge peut être gérée en ambulatoire par un traitement antihypertenseur oral tout en nécessitant un suivi rapproché par la suite. En revanche, l'HTA sévère avec atteinte aiguë d'organe(s) cible(s) nécessite une prise en charge hospitalière immédiate afin de rapidement baisser la tension artérielle à l'aide d'un traitement intraveineux. Cet article a pour but de passer en revue les nouvelles définitions et prises en charge de ces deux entités, et s'adresse autant au médecin praticien installé qu'au médecin hospitalier.

Beyond Atherosclerosis and Fibromuscular Dysplasia: Rare Causes of Renovascular Hypertension.

Renovascular hypertension is one of the most common forms of secondary hypertension. Over 95% of cases of renovascular hypertension are due either to atherosclerosis of the main renal artery trunks or to fibromuscular dysplasia. These two causes of renal artery stenosis have been extensively discussed in recent reviews and consensus. The aim of the current article is to provide comprehensive and up-to-date information on the remaining causes. While these causes are rare or extremely rare, etiologic and differential diagnosis matters both for prognosis and management. Therefore, the clinician cannot ignore them. For didactic reasons, we have grouped these different entities into stenotic lesions (neurofibromatosis type 1 and other rare syndromes, dissection, arteritis, and segmental arterial mediolysis) often associated with aortic coarctation and other arterial abnormalities, and nonstenotic lesions, where hypertension is secondary to compression of adjacent arteries and changes in arterial pulsatility (aneurysm) or to the formation of a shunt, leading to kidney ischemia (arteriovenous fistula). Finally, thrombotic disorders of the renal artery may also be responsible for renovascular hypertension. Although thrombotic/embolic lesions do not represent primary vessel wall disease, they are characterized by frequent macrovascular involvement. In this review, we illustrate the most characteristic aspects of these different entities responsible for renovascular hypertension and discuss their prevalence, pathophysiology, clinical presentation, management, and prognosis.

Interprofessional Medication Adherence Program for Patients With Diabetic Kidney Disease: Protocol for a Randomized Controlled and Qualitative Study (PANDIA-IRIS).

BACKGROUND: Despite effective treatments, more than 30% of patients with diabetes will present with diabetic kidney disease (DKD) at some point. Patients with DKD are among the most complex as their care is multifactorial and involves different groups of health care providers. Suboptimal adherence to polypharmacy is frequent and contributes to poor outcomes. As self-management is one of the keys to clinical success, structured medication adherence programs are crucial. The PANDIA-IRIS (patients diabétiques et insuffisants rénaux: un programme interdisciplinaire de soutien à l'adhésion thérapeutique) study is based on a routine medication adherence program led by pharmacists. OBJECTIVE: The aim of this study is to define the impact of the duration of this medication adherence program on long-term adherence and clinical outcomes in patients with DKD. METHODS: This monocentric adherence program consists of short, repeated motivational interviews focused on patients' medication behaviors combined with the use of electronic monitors containing patients' medications. When patients open the electronic monitor cap to take their medication, the date and hour at each opening are registered. In total, 73 patients are randomized as 1:1 in 2 parallel groups; the adherence program will last 6 months in the first group versus 12 months in the second group. After the intervention phases, patients continue using their electronic monitors for a total of 24 months but without receiving feedback. Electronic monitors and pill counts are used to assess medication adherence. Persistence and implementation will be described using Kaplan-Meier curves and generalized estimating equation multimodeling, respectively. Longitudinal adherence will be presented as the product of persistence and implementation and modelized by generalized estimating equation multimodeling. The evolution of the ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron Modified-Release Controlled Evaluation) and UKPDS (United Kingdom Prospective Diabetes Study) clinical scores based on medication adherence will be analyzed with generalized estimating equation multimodeling. Patients' satisfaction with this study will be assessed through qualitative interviews, which will be transcribed verbatim, coded, and analyzed for the main themes. RESULTS: This study was approved by the local ethics committee (Vaud, Switzerland) in November 2015. Since then, 2 amendments to the protocol have been approved in June 2017 and October 2019. Patients' recruitment began in April 2016 and ended in October 2020. This study was introduced to all consecutive eligible patients (n=275). Among them, 73 accepted to participate (26.5%) and 202 (73.5%) refused. Data collection is ongoing and data analysis is planned for 2022. CONCLUSIONS: The PANDIA-IRIS study will provide crucial information about the impact of the medication adherence program on the adherence and clinical outcomes of patients with DKD. Monitoring medication adherence during the postintervention phase is innovative and will shed light on the duration of the intervention on medication adherence. TRIAL REGISTRATION: Clinicaltrials.gov NCT04190251_PANDIA IRIS; https://clinicaltrials.gov/ct2/show/NCT04190251. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25966.

[Hypertension and cancer†: a close relationship to remember!] / Hypertension artérielle et cancer†: une relation étroite à ne pas oublier†.

Hypertension is a common clinical problem in patients with cancer. This is explained by its high prevalence in the general population, by the improvement in life expectancy in oncology patients thanks to the progress of anti-cancer therapies, but also by cancer therapy, which is sometimes burdened with cardiovascular toxicity. Early detection of hypertension and proper management are crucial to ensure the continuation of oncology treatment and to protect patients from the consequences of hypertension. Renin-angiotensin system blockers and calcium channel blockers are the first-line treatments.

L'hypertension artérielle (HTA) est un problème clinique fréquent chez les patients atteints d'un cancer. Cela s'explique par sa prévalence déjà élevée dans la population générale, par l'amélioration de l'espérance de vie des patients oncologiques grâce aux progrès des thérapies anticancéreuses, mais également par l'utilisation de traitements oncologiques qui sont parfois grevés d'une cardiotoxicité. Un dépistage précoce de l'HTA et une prise en charge adéquate sont alors capitaux afin d'assurer la pérennité des soins oncologiques et protéger les patients des conséquences de l'HTA. Les bloqueurs du système rénine angiotensine et les anticalciques représentent les traitements de première ligne.

[Deprescribing antihypertensive therapy]. / Déprescription dans le contexte de l'hypertension.

With the rise of life-expectancy, the number of comorbidities can increase and lead to polypharmacy (≥ 5 drugs/day) and excessive polypharmacy (> 9 drugs/day). In order to define suitable therapeutic targets, it is essential to take into account the heterogeneity of this population which can be classified into 3 categories : robust, vulnerable or dependent. In this context, the concept of deprescription, which englobes the process of tapering or stopping drugs, aimed at improving patient outcomes, becomes an important therapeutic tool. In the context of hypertension, this approach seems to be a safe, provided that patients can benefit from regular monitoring. It must be considered in vulnerable and dependent patients or patients institutionalized in nursing homes. Although, scientific evidence slowly accumulates, its levels remain moderate. Finally, the deprescribing process, can also be applied in specifics situations in order to prevent adverse events, such as during a heat wave.

Avec le vieillissement de la population, le nombre de comorbidités augmente fréquemment et peut entraîner une polypharmacie (≥ 5 médicaments/jour) ou une polypharmacie excessive (> 9 médicaments/jour). Afin de définir des cibles thérapeutiques adaptées, il est primordial de tenir compte de l'hétérogénéité de cette population que l'on peut schématiquement classer en 3 catégories : robustes, vulnérables et dépendants. Dans ce contexte, la déprescription, le fait d'arrêter ou de réduire la dose d'un médicament, est une action importante qu'il faut connaître et maîtriser. Pour l'hypertension, cette démarche semble être une pratique sûre, à condition, toutefois, que les patients puissent bénéficier d'un suivi régulier. Elle doit être considérée pour les personnes vulnérables et dépendantes, ou les patients institutionnalisés en établissements médico-sociaux. Bien que les évidences scientifiques commencent à s'accumuler, celles-ci restent d'un niveau modéré. Finalement, la déprescription peut également être ponctuelle afin de prévenir les effets indésirables d'une situation particulière, comme lors d'une canicule.

Hypertension and Drug Adherence in the Elderly.

Hypertension is highly prevalent after the age of 65 years affecting more than 60% of individuals in developed countries. Today, there is sufficient evidence from clinical trials that treating elderly subjects with hypertension with antihypertensive medications has a positive benefit/risk ratio even in very elderly patients (>80 years). In recent years, partial or total non-adherence has been recognized as major issues in the long-term management of hypertension in all age categories. However, whether non-adherence is more frequent in hypertensive patients older than 65 years or not is still a matter of debate and the common belief is that adherence is lower in older than in younger patients. Are clinical data supporting this belief? In this brief review, we discuss the topic of drug adherence in elderly in the context of the medical treatment of hypertension. Studies show that drug adherence is actually better in patients aged 65 to 80 years when compared to younger hypertensive patients (<50 years). However, in very old patients (>80 years) the prevalence of non-adherence does increase. In this patients' group, there are specific risk factors for non-adherence such as cognitive ability, depression, and health believes, in addition to classical risk factors for non-adherence. One important aspect in the elderly is the prescription of potentially inappropriate medications that will interfere with the adherence to necessary treatments. In this context, an interesting new concept was developed few years ago, i.e., the process of deprescribing. Thus, today, in addition to conventional guidelines recommendations (use of single pill combinations, individualization of treatments), the evaluation of cognitive abilities, the regular assessment of potentially inappropriate medications, and the process of deprescribing appear to be three new additional steps to improve drug adherence in the elderly and thereby ameliorate the global management of hypertension.

[Arterial hypertension : novelties in 2018]. / Hypertension artérielle.

2018 is the year of the publication of the new European guidelines regarding the management of adult patients with hypertension. These guidelines present several new concepts including a wider use of out-of-office blood pressure measurements, the prescription of dual combinations as first line therapy for most hypertensive patients, a wider use of single pill combinations and a more sustained control of drug adherence with healthcare partners. This article also discusses the new guidelines for the prevention and treatment of orthostatic hypotension and the recently published papers on the risk of skin cancers associated with the long-term use of hydrochlorothiazide (> 5 years).

L'année 2018 est celle de la publication des nouvelles recommandations européennes pour la prise en charge de l'hypertension artérielle chez l'adulte. Ces recommandations présentent plusieurs nouveaux concepts, dont une utilisation plus large de la mesure de la pression artérielle hors du cabinet médical, l'utilisation des combinaisons thérapeutiques en première intention pour la majorité des patients sous la forme d'un seul comprimé et le suivi plus soutenu de l'observance thérapeutique avec les partenaires de santé. Les objectifs à atteindre sont plus stricts (130-140/80 mmHg) pour les patients à haut risque cardiovasculaire et pour les patients de > 65 ans. Cet article résume également les nouvelles recommandations concernant la prévention de l'hypotension orthostatique et les nouvelles publications concernant le risque de cancers cutanés associé à la prise d'hydrochlorothiazide à long terme (> 5 ans).

Blood Pressure and Renal Responses to Orthostatic Stress Before and After Radiofrequency Renal Denervation in Patients with Resistant Hypertension.

BACKGROUND/AIMS: In patients with resistant hypertension, renal denervation (RDN) studies have mainly focused their outcomes on blood pressure (BP). The aim of this study was to evaluate the long-term effect of RDN on neurohormonal profiles, renal hemodynamics and sodium excretion in a resting state and during stress induced by lower body negative pressure (LBNP). MATERIALS AND METHODS: This was a single center prospective observational study. Norepinephrine, plasma renin activity (PRA), glomerular filtration rate (GFR), renal plasma flow (RPF) and sodium excretion were measured in unstimulated conditions (rest) and after one hour of LBNP at three different time points: before (M0), one (M1) and twelve months (M12) after RDN. RESULTS: Thirteen patients with resistant hypertension were included. In the resting state, no differences were observed in norepinephrine, PRA, sodium excretion and mean BP levels after RDN. GFR (78 ± 32 ml/min at M0 vs 66 ± 26 ml/min at M12 (p = 0.012) and filtration fraction (22.6 ±5.4% at M0 vs 15.1 ±5.3% at M12 (p = 0.002)) both decreased after RDN. During LBNP, the magnitude of the mean BP increase was reduced from +6.8 ± 6.6 mm Hg at M0 to +2.3 ± 1.3 mm Hg at M12 (p = 0.005). The LBNP-induced increase in norepinephrine and decrease in GFR and sodium excretion observed before RDN were blunted after the procedure. CONCLUSION: A decrease in GFR and filtration fraction was observed one year after RDN. In addition, our results suggest that RDN blunts not only the norepinephrine but also the mean BP, the GFR and the sodium excretion responses to an orthostatic stress one year after the intervention. REGISTRY NUMBER: NCT01734096.

[Strategies for cardiovascular disease prevention]. / Stratégies de prévention cardiovasculaire au cabinet.

Atherosclerosis is a disease which develops very gradually over decades. Under the influence of modifiable cardiovascular risk factors, such as blood pressure, LDL-cholesterol level, smoking or lifestyle, clinical symptoms of atherosclerosis manifest more or less early in life. When cardiovascular risk factors accumulate, the risk of having a cardiovascular event increases and the benefits of prevention measures are greater. This article summarizes existing strategies for controlling modifiable cardiovascular risk factors in primary prevention. The physician can rely on an interprofessional network of cardiovascular prevention. Managing risk factors while respecting the autonomy and priorities of the patient will bring the greatest benefit.

L'athérosclérose est une pathologie qui se développe sans symptômes sur des dizaines d'années. Sous l'influence de facteurs de risque cardiovasculaire modifiables, tels que la tension artérielle, le taux de LDL-cholestérol, le tabagisme ou le style de vie, les manifestations cliniques de l'athérosclérose apparaissent plus ou moins précocement. Plus les facteurs de risque cardiovasculaire s'accumulent, plus le bénéfice cardiovasculaire est grand lors de la mise en place de mesures de prévention. Cet article résume les stratégies existantes pour contrôler les facteurs de risque cardiovasculaire en prévention primaire. Le médecin peut s'appuyer sur un réseau interprofessionnel ambulatoire de prévention cardiovasculaire. Agir sur l'ensemble des facteurs de risque en respectant l'autonomie et les priorités du patient apportera le plus grand bénéfice.

[Rare vascular diseases, building dedicated multidisciplinary specialized center]. / Maladies vasculaires rares, mise en place d'un centre multidisciplinaire spécialisé au CHUV.

Rare Vascular Diseases (RVD) encompass different types of vessel involvement. Some cause a dilation, others a weakening or tortuosity of the arterial wall, others an obstruction or excessive calcification of arterial walls. Clinical pathway of patients with RVD to diagnosis is often long and complex. Thus, in order to allow early diagnosis and coordinated multidisciplinary management and follow-up, a specialized RVD centre has been set-up at the CHUV, following the framework of the national concept of rare diseases.

Les maladies vasculaires rares (MVR) englobent différents types d'atteintes des vaisseaux. Certaines engendrent une dilatation ou une tortuosité de la paroi artérielle, d'autres une fragilisation de la paroi, d'autres encore entraînent une obstruction du vaisseau, une calcification excessive des parois, ou des malformations vasculaires. Comme pour toutes les maladies rares, le parcours des patients vers un diagnostic est souvent long et complexe. Afin de permettre un diagnostic le plus précoce possible, ainsi qu'un suivi coordonné et une prise en charge multidisciplinaire médicale et sociale, un centre des MVR a été mis en place au CHUV, dans le cadre du concept national des maladies rares.

[Fibromuscular dysplasia and hypertension : beyond renal arteries]. / Hypertension et dysplasie fibromusculaire :au-delà des artères rénales.

Fibromuscular dysplasia (FMD) is a disease associated with abnormalities of the arterial wall of medium-sized arteries. These abnormalities can lead to stenosis or less frequently to dissections or aneurysms. FMD is probably more frequent than initially thought. Nowadays, it is often a chance finding during a radiologic exam. In symptomatic cases, poor organ perfusion due to stenosis, dissection or aneurysm rupture may lead to the diagnosis. The aim of this non-systematic review illustrated with a clinical case is to present our current knowledge of FMD and to highlight the necessity of a standardized and multidisciplinary work-up to improve management of affected patients and understanding of the disease.

La dysplasie fibromusculaire (DFM) est une maladie associée à des anomalies de la paroi des artères de moyen calibre pouvant entraîner des sténoses et plus rarement des anévrismes ou des dissections. Moins rare qu'on ne le pensait initialement, la DFM est parfois découverte fortuitement lors d'un bilan de santé lorsque la maladie est asymptomatique ou lors des manifestations secondaires à l'ischémie de l'organe atteint, conséquence d'une sténose, d'une dissection ou d'une rupture de la paroi artérielle. A partir d'un cas clinique, cette revue non systématique illustre nos connaissances actuelles de la DFM et souligne l'importance d'une prise en charge multidisciplinaire et standardisée pour de meilleurs soins aux patients et une meilleure compréhension de la maladie.

Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study.

BACKGROUND: The ongoing Ebola outbreak led to accelerated efforts to test vaccine candidates. On the basis of a request by WHO, we aimed to assess the safety and immunogenicity of the monovalent, recombinant, chimpanzee adenovirus type-3 vector-based Ebola Zaire vaccine (ChAd3-EBO-Z). METHODS: We did this randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a trial at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Participants (aged 18-65 years) were randomly assigned (2:2:1), via two computer-generated randomisation lists for individuals potentially deployed in endemic areas and those not deployed, to receive a single intramuscular dose of high-dose vaccine (5 × 10(10) viral particles), low-dose vaccine (2·5 × 10(10) viral particles), or placebo. Deployed participants were allocated to only the vaccine groups. Group allocation was concealed from non-deployed participants, investigators, and outcome assessors. The safety evaluation was not masked for potentially deployed participants, who were therefore not included in the safety analysis for comparison between the vaccine doses and placebo, but were pooled with the non-deployed group to compare immunogenicity. The main objectives were safety and immunogenicity of ChAd3-EBO-Z. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02289027. FINDINGS: Between Oct 24, 2014, and June 22, 2015, we randomly assigned 120 participants, of whom 18 (15%) were potentially deployed and 102 (85%) were non-deployed, to receive high-dose vaccine (n=49), low-dose vaccine (n=51), or placebo (n=20). Participants were followed up for 6 months. No vaccine-related serious adverse events were reported. We recorded local adverse events in 30 (75%) of 40 participants in the high-dose group, 33 (79%) of 42 participants in the low-dose group, and five (25%) of 20 participants in the placebo group. Fatigue or malaise was the most common systemic adverse event, reported in 25 (62%) participants in the high-dose group, 25 (60%) participants in the low-dose group, and five (25%) participants in the placebo group, followed by headache, reported in 23 (57%), 25 (60%), and three (15%) participants, respectively. Fever occurred 24 h after injection in 12 (30%) participants in the high-dose group and 11 (26%) participants in the low-dose group versus one (5%) participant in the placebo group. Geometric mean concentrations of IgG antibodies against Ebola glycoprotein peaked on day 28 at 51 µg/mL (95% CI 41·1-63·3) in the high-dose group, 44·9 µg/mL (25·8-56·3) in the low-dose group, and 5·2 µg/mL (3·5-7·6) in the placebo group, with respective response rates of 96% (95% CI 85·7-99·5), 96% (86·5-99·5), and 5% (0·1-24·9). Geometric mean concentrations decreased by day 180 to 25·5 µg/mL (95% CI 20·6-31·5) in the high-dose group, 22·1 µg/mL (19·3-28·6) in the low-dose group, and 3·2 µg/mL (2·4-4·9) in the placebo group. 28 (57%) participants given high-dose vaccine and 31 (61%) participants given low-dose vaccine developed glycoprotein-specific CD4 cell responses, and 33 (67%) and 35 (69%), respectively, developed CD8 responses. INTERPRETATION: ChAd3-EBO-Z was safe and well tolerated, although mild to moderate systemic adverse events were common. A single dose was immunogenic in almost all vaccine recipients. Antibody responses were still significantly present at 6 months. There was no significant difference between doses for safety and immunogenicity outcomes. This acceptable safety profile provides a reliable basis to proceed with phase 2 and phase 3 efficacy trials in Africa. FUNDING: Swiss State Secretariat for Education, Research and Innovation (SERI), through the EU Horizon 2020 Research and Innovation Programme.

Association between obesity and glomerular hyperfiltration: the confounding effect of smoking and sodium and protein intakes.

PURPOSE: Glomerular hyperfiltration has been suggested as a possible mechanism linking obesity and chronic kidney disease (CKD), independently of classical risk factors. We explored the association of overweight and obesity with glomerular hyperfiltration in a large sample of the Swiss adult population, accounting for several confounders including dietary factors. METHODS: Data from a 2010 to 2012 cross-sectional population-based survey in Switzerland were used. Creatinine clearance (CrCl) was determined from 24-h urine collection; CrCl > 140 ml/min was used to define glomerular hyperfiltration. Participants were categorized into lean (<25 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (≥30 kg/m(2)) according to body mass index (BMI). RESULTS: A total of 1339 participants were included in the analysis [median (IQR) age 49.4 (34.3-63.5) years, 48.9 % men]. The prevalences of overweight and obesity were 32.2 and 14.2 %, respectively. Median CrCl was 102[84-121] ml/min in lean, 110 [87-136] ml/min in overweight and 124 [97-150] ml/min in obese participants (p < 0.001). The prevalence of glomerular hyperfiltration increased across BMI categories (10.4, 20.8 and 34.7 %, respectively; p < 0.001). This positive association remained significant after adjusting for age, sex, hypertension, diabetes, smoking and dietary factors (sodium and protein intakes): odds ratio [95 %CI] 2.39 [1.52-3.76] (p < 0.001) for overweight versus lean and 4.10[2.31-7.27] (p < 0.001) for obesity versus lean. CONCLUSIONS: BMI categories and glomerular hyperfiltration are positively associated, independently of other known CKD risk factors and dietary confounders, suggesting that glomerular hyperfiltration may represent an early renal phenotype in obesity. Our observations confirm the significant association of glomerular hyperfiltration with sodium and protein intakes and identify sodium intake as an important modifying factor of the association between hyperfiltration and obesity.